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Norepinephrine transporter inhibition prevents tilt-induced pre-syncope

Item Type:Article
Title:Norepinephrine transporter inhibition prevents tilt-induced pre-syncope
Creators Name:Schroeder, C. and Birkenfeld, A.L. and Mayer, A.F. and Tank, J. and Diedrich, A. and Luft, F.C. and Jordan, J.
Abstract:OBJECTIVES: We tested the hypothesis that pharmacological norepinephrine reuptake transporter (NET) inhibition delays the onset of head-up tilt-induced presyncope in healthy subjects. BACKGROUND: Treatment of neurally mediated syncope is unsatisfactory. In a previous study in a small number of healthy subjects, pharmacologic NET inhibition delayed the onset of head-up tilt-induced pre-syncope. METHODS: We combined data sets from 3 substudies comprising 51 healthy subjects without a history of syncope. In a double-blind, randomized, cross-over fashion, subjects underwent 2 head-up tilt tests, once with placebo and once with a NET inhibitor (sibutramine or reboxetine). Tilt testing was prematurely ended when pre-syncopal symptoms such as dizziness, nausea, or visual disturbances occurred together with a decrease in blood pressure and/or heart rate. RESULTS: The mean tolerated tilt test duration was 29 +/- 2 min with placebo and 35 +/- 1 min with NET inhibition (p = 0.001). The odds ratio for premature abortion of head-up tilt testing was 0.22 (95% confidence interval 0.09 to 0.55, p < 0.001) in favor of NET inhibition. Norepinephrine reuptake transporter inhibition elicited a pressor response and increased upright heart rate. CONCLUSIONS: In healthy subjects, NET inhibition prevents tilt-induced neurally mediated (pre)syncope. Therefore, NET inhibition may be a worthwhile target of drug intervention for larger trials in highly symptomatic patients with neurally mediated syncope.
Keywords:Blood Pressure, Cross-Over Studies, Cyclobutanes, Double-Blind Method, Head-Down Tilt, Heart Rate, Morpholines, Norepinephrine Plasma Membrane Transport Proteins, Posture, Syncope
Source:Journal of the American College of Cardiology
ISSN:0735-1097
Publisher:Elsevier (U.S.A.)
Volume:48
Page Range:516-522
Date:1 August 2006
Official Publication:https://doi.org/10.1016/j.jacc.2006.04.073
PubMed:View item in PubMed

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